An introduction of particles into the vasculature of a patient requires simultaneously satisfying several different concerns or considerations. Depending on the type of particles involved, a concern of significant importance involves preventing the particles from flocculating, i.e. clumping together, as they are being infused or introduced into the vasculature. This is of particular concern in the case of stem cells which can flocculate, but which are most effective in therapy if left to function either as individual cells or in small groups of cells. An additional benefit of preventing particles from flocculating is the prevention of heart attacks which may be caused when clumps of cells are introduced into the coronary circulatory system. Also, it is possible that the retention rate of stem cells in the heart, or other targeted tissue, will increase when the stem cells are infused while blood flow is slow in the circulatory system.
In all types of intravascular therapy (i.e. intracoronary, intra-arterial or intravenous), it is always an essential concern that the therapeutic agent (e.g. biologics or drugs) be infused or delivered in a predictably controlled manner. Furthermore, it is important that the therapeutic agent be effectively delivered to a proper destination in the vasculature. All of this involves dosage and delivery rate considerations. Moreover, it requires careful handling of the therapeutic agent to insure it (the therapeutic agent) is not damaged or otherwise compromised during an infusion.
From a mechanical perspective, it is known that the diameter of a fluid passageway is a factor that will affect the rate of fluid flow through the passageway. For protocols where small groups of de-flocculated particles are to be infused into a vessel of a vasculature, the diameter of the passageway must obviously be large enough to individually accommodate the small groups of particles. On the other hand, it must also be small enough to separate and prevent larger groups of particles (cells) from clinging to each other. A consequence of this is that the rate at which particles can be carried through the passageway will be circumscribed by the dimensions of the passageway. A further consequence of this is that, as particles leave the passageway, they are then influenced by the flow of fluid (i.e. blood) in the vessel of the vasculature. Depending on the purpose of the protocol, this may mean that the downstream fluid flow in the vasculature will somehow also need to be regulated.
In some cases, the downstream fluid flow in the vasculature (discussed above) can be controlled or regulated using an inflatable balloon that is attached to an outside surface of the catheter tube. For these and similar arrangements, when the balloon is deployed at the treatment site (i.e. inflated), a pressure is exerted on the catheter tube. The catheter tube, however, is typically made of a flexible material to allow it to twist and turn as the catheter is navigated through the patient's vasculature. Because of the flexible nature of the catheter tube, it is typically susceptible to kinking and/or collapse during inflation of the balloon. This can be particularly troublesome for infusion catheters where the material to be infused is pumped through a central lumen of the catheter tube. In this instance, a collapse or even partial blocking of the central lumen where the balloon is inflated can impede fluid flow in the central lumen, and adversely affect an infusion procedure. In addition to reducing flow, a collapsed or blocked catheter tube lumen can reduce cell viability during transport through the lumen by exposing the cells to shear stress (Note: in some cases, viability has been found to be lowered by around 70-80% when flow is impeded in the central lumen).
For each type of cell or cell family, there is a shear stress threshold which must be avoided to prevent cell injury. For some types of cells, exposure to stresses above a maximum shear stress is sufficient to avoid damage. For other types of cells, both the magnitude of the shear stresses and the time the cell is exposed to the shear stress must be considered when establishing the shear stress threshold.
A number of factors can influence the shear stress levels that develop when a fluid medium having a suspension of cells is pumped through an infusion catheter and introduced into the vasculature of a patient. These factors can include the size and geometry of the internal passages in the catheter, the concentration and type of cells present in the fluid medium and the flow rate. For example, the use of a multi-lumen separator in an infusion catheter can, in some cases, affect the levels of shear stress that are developed within the catheter. In addition, as described above, the use of an inflation balloon can in some cases, affect the size and geometry of the internal passages in the catheter, which in turn, can affect the levels of shear stress that are developed.
In light of the above, it is an object of the present invention to provide an infusion system that can effectively introduce only small groups of particles into a fluid flow. Another object of the present invention is to provide an infusion system that coordinates the flow rate of a particle/fluid medium (i.e. a first fluid) with the flow rate of a fluid (i.e. a second fluid) into which the particle/fluid medium is being introduced. Still another object of the present invention is to provide an infusion system that produces a low exit pressure to reduce the impact on a vessel wall caused when fluid exits a catheter and enters the vessel. It is still another object of the present invention to provide an infusion system having a balloon to regulate blood flow at an infusion site that is not subject to central lumen collapse or blocking during balloon inflation. It is yet another object of the present invention to provide an infusion protocol which ensures that stresses exerted on an infusion fluid are maintained below a shear stress threshold specified for the type of cells present in the infusion fluid to prevent cell damage during an infusion procedure. It is another object of the present invention to provide a method for determining suitable influsion flow rates and fluid medium cell concentrations for a particular catheter size and geometry that will ensure that stresses exerted on an infusion fluid are maintained below a shear stress threshold specified for the type of cells present in the infusion fluid to prevent cell damage during an infusion procedure. Yet another object of the present invention is to provide a method for infusing stem cells that is easy to use, is simple to implement and is comparatively cost effective.